Based on new evidence from our laboratory, which has discovered an important inhibitory role of the ventromedial nucleus of the hypothalamus (VMH) in maternal behavior, the objective of this grant proposal is to elucidate the involvement of the VMH in the onset of maternal behavior. The experiments described in the present grant proposal will use behavioral, molecular, and anatomical approaches to identify the possible mechanisms of action of the VMH on the inhibition of maternal behavior. The hypothesis underlying the present proposal is that under normal physiological conditions the VMH inhibits the display of maternal behavior in virgin and late-pregnant rats by inhibiting the actions of the medial preoptic area (MPOA, an area considered to be crucially involved in the display of maternal behavior). The specific aim of the first three experiments will be to examine the role of the VMH in the regulation of maternal behavior in estradiol-primed, virgin rats. Experiment 1 will analyze the timing of neurotoxin administration into the VMH and subsequent maternal behavior stimulation. Experiment 2 will determine if infusions of the sodium channel blocker, tetrodotoxin, will stimulate short-latency maternal behavior, while experiment 3 will examine the role of GABA infusions into the VMH and subsequent maternal behavior. The second specific aim is to determine the changes in receptor gene expression of the key pregnancy hormones, estrogen, progesterone, and prolactin, in estradiol-primed, virgin rats. Experiments 4,5 and 6 will use in situ hybridization histochemistiy (ISHH) to determine the changes in estrogen, progesterone, and prolactin receptor gene expression, respectively, in the VMH and MPOA following estradiol stimulation in virgin rats. These 3 experiments will also investigate the changes in receptor gene expression in the MPOA following neurotoxic lesions to the VMH. The third specific aim is to determine, using anatomical, track-tracing methods, whether neurons in the VMH that are activated in the presence of pups project to the MPOA (experiment 7). Experiment 8 will determine the neurotransmitter involved in the regulation of the MPOA by the VMH. Together, these studies will help elucidate the role of the VMH in maternal behavior in virgin rats and identify the neural basis of parental care.